Exaggerated airway narrowing in response to bronchoconstricting stimuli is a characteristic feature of asthmatic subjects. It is unknown whether the site of airway narrowing differs in asthmatic subjects from that observed in normal subjects. Increased airway wall thickness has been suggested as a contributing cause for airway hyperresponsiveness in asthma, based on histologic measurements. We measured airway wall thickness and the site and magnitude of airway narrowing in response to inhaled methacholine in normal subjects and in patients with mild to moderate asthma using high resolution computed tomography (HRCT). After a comparable decrease in FEV1, there were no differences in the site or magnitude of airway narrowing for any category of airway size in asthmatic subjects and normals. However, the results show that the smaller airways of the asthmatic subjects are significantly thickened and that the airway wall area does not change after bronchoconstriction whereas it decreases in normal subjects. We conclude that airway wall thickening and the lack of a change in airway wall dimensions following bronchoconstricting stimuli could contribute to exaggerated airway narrowing in asthma.